Toward Precise Risk Stratification after the Functional Cure of Chronic Hepatitis B

Chronic hepatitis B remains a major global health challenge despite the advances in antiviral therapy. Although hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure, liver-related complications, particularly hepatocellular carcinoma, may still occur after viral clearance. This residual risk reflects the lasting impact of host and liver factors rather than ongoing viral activity. Conventional prediction models have attempted to stratify the residual risk after a functional cure but remain limited in their ability to guide individualized management. Recent advances in machine learning have enabled more precise risk stratification by capturing complex host-driven determinants of the long-term outcomes. These approaches support a shift from uniform surveillance toward risk-adaptive monitoring strategies. Nevertheless, post-cure management is emerging as a new clinical priority as more patients achieve a functional cure. Therefore, a functional cure should be viewed not as the end of the disease, but as the beginning of a phase requiring personalized risk assessment and surveillance.